Shi Wei, Qiu Xin, Huang Liang, Zeng Linan, Lu Runxin, Li Hailong, Zou Kun, Jia Zhijun, Cheng Guo, Yu Qin, Zhao Limei, Zhang Lingli
NMPA Key Laboratory for Technical Research On Drug Products In Vitro and In Vivo Correlation, Chengdu, 610041, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, 610041, China.
Eur J Clin Pharmacol. 2025 Mar;81(3):395-401. doi: 10.1007/s00228-024-03792-5. Epub 2025 Jan 7.
The potential nephrotoxicity of cyclosporine A (CsA) has been a problem for treating graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the relationship between CsA blood concentration and acute kidney injury (AKI) in pediatric patients after allo-HSCT remains unclear.
We performed a retrospective study including pediatric patients who received allo-HSCT in West China Second Hospital of Sichuan University from 2000 to 2022 and collected their clinical data. Included patients' CsA blood concentration were divided into three cohorts according to the guideline. Multivariate logistic regression was used to estimate the relationship between AKI and CsA blood concentration and other factors. And the maximum cut-off value for the safe blood concentration range of CsA was obtained by the receiver operating characteristic (ROC) curve.
Seventy-nine patients (average age 6.75 ± 4.25) were included. The incidence of kidney injury for three CsA blood concentration cohorts (< 200 ng/ml, 200-300 ng/ml, > 300 ng/ml) were 21.30%, 23.50%, and 66.70%, respectively. A multivariate logistic regression identified CsA blood concentration (> 300 ng/ml) and infection were risk factors for AKI (OR : 0.115, 95% CI: 0.029-0.458; OR : 0.184, 95% CI: 0.036-0.929; OR : 5.006, 95% CI: 1.491-16.810). Meanwhile, the maximum cut-off value for the safe blood concentration range of CsA is 276.85 ng/ml with an AUC value of 0.684 (P = 0.010).
In conclusion, clinical treatment for the pediatric patients after allo-HSCT may be considered to control the blood concentration of CsA in 200-276.85 ng/ml and closely monitoring patients who have infections.
环孢素A（CsA）潜在的肾毒性一直是异基因造血干细胞移植（allo-HSCT）后治疗移植物抗宿主病（GVHD）的一个问题。然而，allo-HSCT后儿科患者中CsA血药浓度与急性肾损伤（AKI）之间的关系仍不清楚。
我们进行了一项回顾性研究，纳入了2000年至2022年在四川大学华西第二医院接受allo-HSCT的儿科患者，并收集了他们的临床数据。根据指南将纳入患者的CsA血药浓度分为三个队列。采用多因素logistic回归分析评估AKI与CsA血药浓度及其他因素之间的关系。通过受试者工作特征（ROC）曲线得出CsA安全血药浓度范围的最大截断值。
共纳入79例患者（平均年龄6.75±4.25岁）。三个CsA血药浓度队列（<200 ng/ml、200 - 300 ng/ml、>300 ng/ml）的肾损伤发生率分别为21.30%、23.50%和66.70%。多因素logistic回归分析确定CsA血药浓度（>300 ng/ml）和感染是AKI的危险因素（OR：0.115，95%CI：0.029 - 0.458；OR：0.184，95%CI：0.036 - 0.929；OR：5.006，95%CI：1.491 - 16.810）。同时，CsA安全血药浓度范围的最大截断值为276.85 ng/ml，AUC值为0.684（P = 0.010）。
总之，对于allo-HSCT后的儿科患者，临床治疗可考虑将CsA血药浓度控制在200 - 276.85 ng/ml，并密切监测有感染的患者。
